This proposal seeks infrastructure support only for core functions to conduct 5 years of continued follow-up of the Women's Health Study (WHS), under PAR-17-233. The WHS began in 1992 as a randomized trial testing aspirin, beta-carotene, and vitamin E for prevention of cancer and cardiovascular disease (CVD) in 39,876 healthy women over age 45. Prior to randomization, 28,345 women (71%) provided a blood sample: all have been assayed for a wide range of biomarkers; genome-wide association studies (GWAS) have been completed on >25,000, and exome chip genotyping on >22,000. The trial ended in 2004, and 33,682 (or 89% of surviving women were willing to be followed observationally. Women report via yearly questionnaires on a wide range of exposures and endpoints; we confirm self-reported cancer and CVD endpoints with medical records, and cause of death by medical records and/or death certificates. Device-assessed 7-day physical activity and sedentary behavior has been collected on 17,708 women. The WHS is unique in having extensive genetic data as well as objectively-assessed physical activity and sedentary behavior in such a large cohort. Follow-up is excellent: after almost 24 years, morbidity follow-up is still 89.6%% and mortality follow-up is virtually 100%. As the average age of living participants is 77.1 years, event rates are increasing substantially: at the end of current funding (8/31/19), 7,769 confirmed cancers will have occurred; by the end of the proposed funding cycle (8/31/24), 10,869 cancers will be confirmed. This will substantially increase WHS's ability to address important cancer questions, including examination of site-specific cancers, rare cancers, and tumor- specific characteristics. The WHS has actively shared data with internal and external researchers, resulting in 650 papers published, 106 funded grants using WHS data, and collaboration in 22 NCI Cohort Consortium projects. Currently, none of the ancillary studies provides funding for ascertainment and validation of cancer (and CVD) endpoints. In the proposed funding period, we will continue the WHS infrastructure, including the follow-up and evaluation of self-reported exposures and endpoints, and maintenance of the WHS biospecimen repository, to further facilitate data sharing and collaboration. WHS is also committed to continuing to provide leadership in research aims related to gene-based prediction of incident disease and gene-environment interactions; improved assessments of physical activity and sedentary behavior to study associations with health outcomes, and evaluation of long-term chemoprotection of low-dose aspirin. Independent funding will be sought over the next period to address specific hypotheses in these areas. In the next 5 years, continued infrastructure support and follow-up is crucial for maximizing the cost-effective use of this valuable large-scale cancer cohort of women with a rich resource of already collected phenotypic and genetic data, particularly since many WHS findings have been and can be directly translated to clinical and public health practice or formal recommendations.